Radionuclides, meaning atomic species that exhibit radioactivity, are useful for diagnostic and therapeutic techniques such as tumor imaging and radiotherapy of tumors. Such techniques have increased the demand for available supplies of carrier-free radionuclides having reasonable half lives such as Technetium-99m (Tc-99m, half-life 6.02 hours) used for diagnostic purposes. One method of obtaining such radionuclides is via extraction of a "daughter" radionuclide which is a decay product of a longer-lived ("parent") radionuclide. For example, Tc-99m is the daughter radionuclide of molybdenum-99 (Mo-99, half-life 66.02 hrs).
Devices known as generators are commercially available to provide separation of a daughter radionuclide from its parent radionuclide to provide a supply of the relatively short-lived daughter isotope. The parent and daughter radionuclides may be separated using chromatographic, solvent extraction, or sublimation generators. The chromatographic generators, due to their simplicity and compact nature, are more convenient to use in hospitals and other institutions where radionuclides are used for diagnosis and therapy. For use in such generators, the parent radionuclide should have a sufficient long half-life to provide enough time for transit and storage prior to commencing the extraction procedure.
Chromatographic generators, such as those used to produce Tc-99m from Mo-99, typically contain insolubilized parent radionuclide adsorbed onto a bed or column of material such as aluminum oxide ("alumina") for which the daughter radionuclide has relatively little affinity. The daughter radionuclide, which forms from decay of the parent, is then periodically eluted from the column, for example using physiological saline. Typically, the daughter radionuclide product will be of high specific activity and is referred to as "carrier free" since it is produced by beta decay of a parent radionuclide, and the product is relatively free of stable isotopes of the daughter radionuclide.
Until recently, prior chromatographic generators were only able to provide high specific activity product radionuclides at relatively low concentrations from low specific activity (n,.gamma.) parent radionuclides such as Mo-99 due to the necessity of using large quantities of alumina and eluting solution to obtain the daughter radionuclide. As a result, fission-produced parent radionuclides have been preferred for producing radionuclides such as Tc-99m. Unfortunately, fission-produced radionuclides require complex facilities and safety precautions that entail high costs relative to the amount of daughter radionuclide produced.
Recently, a chromatographic Mo-99/Tc-99m generator has been developed that employs a matrix composed of zirconium molybdate containing Mo-99. Evans et al., U.S. Pat. No. 4,280,053. This matrix is said to be essentiallyl non-elutable, and to allow the Tc-99m produced in the matrix to diffuse through and from the matrix during elution.
Another radionuclide which shows promise for therapeutic and diagnostic applications is Rhenium-188 (Re-188), a decay product of tungsten-188 (W-188), a low specific activity isotope produced from naturally occurring tungsten (W-186).
Although the chemical properties of rhenium ae not as well known as those of technetium, certain of its properties suggest it may be suited for use in radiotherapeutic applications, for example, as a label for conjugation to monoclonal antibodies for targeting to tumors. Re-188 (half-life 16.98 hours) has a longer half-life than Tc-99m (6.02 hours), possesses a strong particulate emission (beta energy of 2.12 MeV) (in contrast, Tc-99m has no particulate emission), and has an imageable gamma emission (15%, 155 keV) ideal for current gamma camera imaging of tumors. W-188 radionuclide is derived from either natural tungsten (W-186) or, preferably, from a target tungsten material enriched in W-186 by double neutron capture using a high-flux reactor. The nuclear properties of this isotopic system are as follows: ##STR1##
Previous tungsten/rhemium generators have consisted of small, alumina columns with relatively small amounts of tungsten targets adsorbed on the columns and, thus, low rhenium yields in the microcurie (.mu.Ci) range. To increase the amount of rhenium obtainable from such columns, (i.e., in the millicurie range, mCi) larger column masses are necessary in order to contain larger amounts of target tungsten. These larger columns, in turn, require increased eluting volumes.
In addition, prior W-188/Re-188 generators using alumina columns have provided poor yields of Re-188 and unacceptable levels of release, or "breakthrough" of W-188 from the column due primarily to the necessity of adsorbing large (0.5-2.0 grams) amounts of target tungsten (primarily as W-186) onto the alumina column. A W-188/Re-188 generator system incorporating larger amounts of target tunsten to produce high yields (millicuries) of carrier-free Re-188 in small volumes (milliliters) without significant W-188 contamination, would be useful for therapeutic and diagnostic applications.